Fact-checked by Grok 2 weeks ago

Myotonic dystrophy

Myotonic dystrophy is a group of inherited multisystem disorders characterized by progressive muscle weakness and wasting, delayed relaxation of muscles after contraction (myotonia), and involvement of non-muscular tissues such as the heart, eyes, gastrointestinal tract, endocrine system, central nervous system, and increased cancer risk.^[1] It represents the most common form of muscular dystrophy in adults, with an estimated prevalence of approximately 1 in 8,000–20,000 individuals worldwide for type 1 and lower (about 1 in 50,000) for type 2.^[1] There are two genetically distinct forms: myotonic dystrophy type 1 (DM1), caused by an expansion of CTG repeats in the DMPK gene on chromosome 19, and myotonic dystrophy type 2 (DM2), resulting from CCTG repeat expansions in the CNBP gene on chromosome 3; both are inherited in an autosomal dominant pattern with anticipation, where symptoms often worsen in successive generations due to increasing repeat lengths. DM1 typically presents with more severe and varied symptoms, including congenital forms with hypotonia and respiratory issues in infants, distal muscle weakness in adults (such as grip myotonia and foot drop), early cataracts, cardiac conduction defects that can lead to arrhythmias or sudden death, hypersomnia, cognitive impairments, and endocrine abnormalities like insulin resistance or testicular atrophy.^[1] In contrast, DM2 is generally milder, with prominent proximal muscle weakness, myalgia, stiffness, and less frequent cardiac or cognitive involvement, though it still features myotonia and cataracts; it rarely manifests before age 20 and lacks a congenital form.^[2] Diagnosis is confirmed through genetic testing to detect the repeat expansions, as clinical features overlap with other myopathies but the multisystem nature and family history are key indicators.^[3] Management is symptomatic and multidisciplinary, focusing on monitoring and treating complications: physical therapy to maintain mobility, cardiac evaluations with electrocardiograms to prevent arrhythmias, ophthalmologic care for cataracts, respiratory support if needed, and genetic counseling for families due to the high risk of transmission and variable expressivity.^[1] There is no cure, but as of 2025, ongoing research into antisense oligonucleotides and gene therapies, including FDA Fast Track designations for candidates like SAR446268, shows promise for addressing the underlying RNA toxicity caused by the repeat expansions.^[4] The condition's impact extends beyond physical symptoms, often affecting quality of life through fatigue, pain, and psychosocial challenges.^[5]

Overview

Definition and Classification

Myotonic dystrophy (DM) is an autosomal dominant neuromuscular disease characterized by myotonia—a delayed relaxation of muscles after contraction—progressive muscle weakness, and multisystem involvement affecting the cardiac, respiratory, endocrine, and central nervous systems, among others.^[6]^[1] It represents the most common form of adult-onset muscular dystrophy, with recent estimates indicating a prevalence of about 1 in 2,100 individuals worldwide as of 2023.^[7] Unlike many other muscular dystrophies driven by protein dysfunction, DM's core pathogenesis stems from RNA toxicity, where expanded nucleotide repeats in specific genes produce aberrant RNA transcripts that disrupt cellular processes such as RNA splicing.^[8]^[9] DM is classified into two primary genetic forms: type 1 (DM1), the more prevalent variant caused by an unstable CTG trinucleotide repeat expansion in the 3' untranslated region of the DMPK gene on chromosome 19, and type 2 (DM2), resulting from a CCTG tetranucleotide repeat expansion in intron 1 of the CNBP (also known as ZNF9) gene on chromosome 3.^[10]^[11] Both forms are inherited in an autosomal dominant manner with anticipation, where repeat expansions tend to increase in successive generations, leading to earlier onset and greater severity.^[1]^[2] No confirmed third form (DM3) has been genetically identified, despite early suggestions of a potential locus on chromosome 15.^[12] Historically, DM1 was first described in 1909 by German physician Hans Steinert as "dystrophia myotonica," later termed Steinert's disease, recognizing its distinctive combination of muscle stiffness and wasting.^[13] This naming evolved with the identification of DM2 in 2001, leading to the unified classification of myotonic dystrophies as RNA-mediated disorders distinct from protein-based dystrophies like Duchenne or Becker types.^[6]^[14]

Key Characteristics

Myotonic dystrophy is a multisystem disorder primarily characterized by progressive skeletal muscle weakness and myotonia, which manifests as delayed relaxation of muscles following contraction, often elicited by grip or percussion testing.^[6] Additional hallmark features include early-onset cataracts, cardiac conduction defects that can lead to arrhythmias, and insulin resistance contributing to metabolic disturbances.^[15] These symptoms typically emerge in adulthood, though severity varies, establishing myotonic dystrophy as the most common adult-onset muscular dystrophy.^[16] The condition follows an autosomal dominant inheritance pattern with variable penetrance, meaning affected individuals have a 50% chance of transmitting the mutation to each offspring, but clinical expression can range from mild to severe.^[1] A distinctive feature is the anticipation phenomenon, where the disease worsens in severity and onset age across generations, attributed to the expansion of trinucleotide repeats during germline transmission.^[17] In myotonic dystrophy type 1 (DM1), this risk is particularly high in newborns from maternally affected parents, potentially resulting in congenital forms.^[1] Beyond skeletal muscle, myotonic dystrophy exhibits multisystemic involvement, affecting smooth muscle function such as gastrointestinal motility disorders, central nervous system features like cognitive impairment and excessive daytime sleepiness, and endocrine systems including testicular atrophy and hypothyroidism.^[15] This broad organ impact underscores the disorder's complexity, often requiring multidisciplinary management.^[6] At the molecular level, the primary pathogenic mechanism is a toxic gain-of-function of mutant RNA containing expanded nucleotide repeats, which forms nuclear foci and sequesters RNA-binding proteins such as muscleblind-like (MBNL) proteins, disrupting alternative splicing and other RNA processing events essential for cellular function.^[9] This RNA toxicity model explains the shared clinical phenotypes across myotonic dystrophy types despite distinct genetic loci.^[16]

Signs and Symptoms

Type 1 Myotonic Dystrophy (DM1)

Type 1 myotonic dystrophy (DM1) is the most prevalent form of myotonic dystrophy, characterized by a broad spectrum of clinical manifestations that vary significantly by age of onset, ranging from severe congenital presentations to milder adult-onset cases. The disorder primarily affects skeletal muscles but involves multiple organ systems, with symptoms including progressive muscle weakness, myotonia (delayed muscle relaxation after contraction), and extrasomatic features such as cataracts and cardiac conduction defects. Severity correlates inversely with age of onset, with earlier presentations often linked to larger genetic expansions, though this is detailed elsewhere.^[1] In the congenital form of DM1, which occurs when the affected parent (typically the mother) transmits the mutation, infants present with profound hypotonia, often described as "floppy baby" syndrome, leading to respiratory distress and inadequate ventilation shortly after birth. Common features include talipes equinovarus (clubfoot), feeding and swallowing difficulties due to weak oropharyngeal muscles, and delayed developmental milestones such as motor skills and speech. This form carries a high risk of mortality in infancy from respiratory failure or complications, though survival rates have improved with intensive neonatal care, including mechanical ventilation and gastrostomy feeding. Survivors frequently exhibit persistent cognitive and motor impairments into childhood.^[18]^[19] Childhood-onset DM1, emerging between ages 1 and late adolescence, manifests milder physical symptoms than the congenital variant but prominently features cognitive and behavioral challenges. Affected individuals often display intellectual impairment with IQ scores typically in the mild to moderate range, alongside attentional deficits, executive dysfunction, and learning difficulties that impact school performance. Behavioral issues, such as apathy, avoidance, or obsessive-compulsive traits, are common and may precede overt muscle symptoms. Physical signs include early-onset cataracts by the second decade, subtle myotonia in the hands or face, and gradual distal weakness; cardiac arrhythmias can also appear, sometimes triggered by physical exertion.^[20]^[19] Adult-onset DM1, the classic presentation, typically begins after age 20 and progresses insidiously, starting with distal muscle weakness in the hands, forearms, and lower legs (foot drop), alongside facial and neck muscle involvement. Characteristic facial features include ptosis (drooping eyelids), temporal wasting, and a "hatchet face" appearance due to masseter and temporalis atrophy; myotonia is evident as grip release delays or percussion-induced stiffness in the face, tongue, and limbs. Early posterior subcapsular cataracts are a hallmark, often detectable by slit-lamp exam in the third or fourth decade.^[21]^[1] Systemic involvement in DM1 spans all onset forms and contributes substantially to morbidity. Cardiac manifestations include conduction abnormalities such as atrioventricular (AV) block, risking sudden death and necessitating routine electrocardiographic monitoring. Respiratory muscle weakness leads to alveolar hypoventilation, particularly during sleep, increasing susceptibility to infections and requiring ventilatory support in advanced stages. Gastrointestinal dysmotility causes dysphagia, constipation, and diarrhea, while endocrine issues encompass hypogonadism with testicular atrophy in males and irregular menses in females. Central nervous system effects involve cognitive impairment, particularly executive dysfunction, daytime somnolence, and increased pain sensitivity.^[1]^[22]^[19] The disease progresses slowly over decades, with muscle weakness and wasting advancing to wheelchair dependence in many by midlife, while myotonia may lessen with age due to increasing weakness. Life expectancy is reduced, primarily from respiratory or cardiac complications, though management can mitigate this.^[22]^[21]

Type 2 Myotonic Dystrophy (DM2)

Type 2 myotonic dystrophy (DM2), also known as proximal myotonic myopathy, is characterized by a generally milder phenotype than type 1 myotonic dystrophy (DM1), with symptoms typically emerging in adulthood and involving primarily proximal muscle groups.^[2] The disorder manifests as slowly progressive proximal muscle weakness, particularly affecting the thighs and shoulders, with notably less involvement of facial and distal muscles compared to the more severe distal and facial weakness seen in DM1.^[11] Myotonia in DM2 is often mild and may be limited to grip myotonia or even absent in early stages, contrasting with the more prominent and widespread myotonia in DM1.^[23] Unlike DM1, DM2 lacks congenital or severe childhood presentations, with onset usually occurring between ages 20 and 60, most commonly in the 30s to 50s.^[2] Cataracts typically develop later, often in the fourth or fifth decade, and cognitive impairment, if present, is minimal and subtle, without the significant intellectual disability associated with DM1.^[11] Systemic features of DM2 include cardiac conduction abnormalities, such as atrioventricular block, which are less frequent and severe than the life-threatening arrhythmias in DM1.^[23] Respiratory involvement is mild, potentially leading to diaphragmatic weakness but rarely requiring ventilation support.^[2] Metabolic disturbances resembling features of metabolic syndrome are common, including hyperinsulinemia, glucose intolerance, and an increased risk of obesity, alongside occasional hypersomnia that can contribute to daytime fatigue.^[11] Women with DM2 often experience earlier menopause, though severe hypogonadism is not typical.^[23] The progression of DM2 is slower than in DM1, frequently stabilizing in adulthood and allowing for relatively preserved overall function and mobility into later years.^[2] However, chronic muscle pain (myalgia) and fatigue are prevalent and can significantly impact quality of life, often becoming prominent early in the disease course.^[11]

Genetics

DM1 Genetic Mechanisms

Myotonic dystrophy type 1 (DM1) is caused by an unstable expansion of a CTG trinucleotide repeat in the 3' untranslated region of the DMPK gene, located on chromosome 19q13.3.^[1] Normal alleles contain 5 to 34 CTG repeats, while alleles with more than 50 repeats are pathogenic, and those exceeding 1,000 repeats are typically associated with the congenital form.^[1] ^[24] DM1 follows an autosomal dominant inheritance pattern characterized by anticipation, in which the CTG repeat expansion increases across generations, leading to earlier onset and increased severity in offspring.^[24] This phenomenon is particularly pronounced with maternal transmission, where large expansions are more likely to occur, often resulting in congenital DM1 when transmitted from affected mothers.^[1] Paternal transmission tends to involve smaller expansions, with a lower risk of the congenital phenotype.^[24] At the molecular level, the expanded CTG repeats in the DMPK transcript produce RNA with elongated CUG repeats, which exert toxic effects by sequestering RNA-binding proteins essential for normal cellular function (mechanisms detailed in pathophysiology sections).^[1] Additionally, somatic mosaicism arises from the instability of the repeat sequence in non-germline tissues, resulting in varying repeat lengths across different cell types and contributing to the disease's variable expressivity.^[1] ^[25] Genotype-phenotype correlations in DM1 are largely determined by the size of the CTG expansion, with longer repeats predicting greater disease severity.^[24] For instance, expansions of 50 to 150 repeats typically correspond to mild adult-onset disease with late manifestation of symptoms, 200 to 1,000 repeats to classical or juvenile-onset forms, and over 1,000 repeats to severe congenital DM1 with high infant mortality.^[1] ^[24] However, these correlations are approximate due to factors like somatic instability and modifier genes.^[25] Genetic testing for DM1 involves polymerase chain reaction (PCR), triplet repeat-primed PCR (TP-PCR), Southern blot analysis, and emerging next-generation sequencing (NGS) methods to quantify CTG repeat length, establishing diagnostic thresholds: fewer than 35 repeats as normal, 35 to 49 as premutation (reduced penetrance), and 50 or more as full mutation with complete penetrance.^[1] ^[26] These results are essential for family counseling, enabling assessment of transmission risks—up to 100% penetrance in offspring of affected individuals—and guiding reproductive decisions, such as prenatal testing for at-risk pregnancies.^[1] Early identification through testing also facilitates predictive counseling for asymptomatic carriers with intermediate alleles.^[24]

DM2 Genetic Mechanisms

Myotonic dystrophy type 2 (DM2) is caused by an unstable CCTG tetranucleotide repeat expansion located in intron 1 of the cellular nucleic acid-binding protein (CNBP) gene, also known as zinc finger protein 9 (ZNF9), on chromosome 3q21.^[14] Normal alleles contain fewer than 30 CCTG repeats, while pathogenic expansions range from 75 to more than 11,000 repeats, with a mean of approximately 5,000 in affected individuals.^[14]^[27] This intronic expansion leads to the production of mutant RNA transcripts containing expanded CCUG repeats, which exert a toxic gain-of-function effect by sequestering RNA-binding proteins and disrupting alternative splicing, similar to the RNA toxicity mechanism in DM1 but resulting in a generally milder phenotype.^[28] The intronic position of the repeat minimizes direct interference with CNBP protein coding, contributing to the less severe clinical manifestations compared to exonic disruptions in other disorders.^[23] DM2 follows an autosomal dominant inheritance pattern, with each child of an affected individual having a 50% risk of inheriting the expanded allele.^[2] Unlike DM1, DM2 exhibits reduced anticipation, as the expansions are more stable across generations and show lower rates of intergenerational expansion or contraction.^[29] Congenital DM2 cases are exceedingly rare, in contrast to the frequent congenital presentation in DM1.^[2] However, high somatic mosaicism is observed, with significant variability in repeat length across tissues, including progressive expansion in muscle over time.^[30] Genotype-phenotype correlations in DM2 are weaker than in DM1, with no strict relationship between repeat length and overall disease severity or age of onset.^[2] Repeat size does not reliably predict specific symptoms like myotonia or cataracts. This variability complicates prognostic assessments but underscores the role of modifier factors beyond repeat length. Detecting the DM2 expansion presents technical challenges due to the large size and repetitive nature of the CCTG tract, which often resists amplification by standard PCR methods.^[2] Normal alleles frequently contain interruptions such as NCTG motifs within the complex repeat structure [(TG)_n (TCTG)_n (CCTG)_n], which can further hinder precise sizing and lead to underestimation of expansion length in diagnostic assays.^[30] Emerging long-read sequencing approaches are improving detection of these complex repeats. These detection issues have implications for genetic counseling, as the stable transmission and incomplete penetrance in premutation carriers (approximately 30-55 repeats) necessitate careful discussion of risks, including potential late-onset symptoms and family planning options; alleles with 55-74 repeats are of uncertain significance.^[2]

Pathophysiology

Molecular Pathogenesis

Myotonic dystrophy (DM) is primarily driven by a toxic RNA gain-of-function mechanism, where expanded nucleotide repeats in non-coding regions of the DMPK gene (for DM1) or CNBP gene (for DM2) produce mutant RNAs that disrupt RNA processing. In DM1, the CTG trinucleotide repeat expansion in the 3' untranslated region of DMPK generates CUG repeat-containing RNA transcripts that fold into stable hairpin structures.^[9] These hairpins sequester RNA-binding proteins, notably muscleblind-like (MBNL) family members such as MBNL1, into discrete nuclear foci detectable by fluorescence in situ hybridization (FISH).^[31] Similarly, in DM2, the intronic CCTG tetranucleotide repeat expansion in CNBP yields CCUG repeat RNA with analogous hairpin formation and MBNL sequestration, though the repeats are typically longer (average 2,500–12,000 units) compared to DM1 (50–4,000 CTG units).^[32] This RNA toxicity model, first elucidated through studies of MBNL knockout mice recapitulating DM splicing defects, underscores the central role of aberrant RNA-protein interactions in disease pathogenesis.^[33] The sequestration of MBNL proteins impairs their normal function in regulating alternative splicing, leading to widespread missplicing of pre-mRNAs across multiple tissues. Key examples include the chloride channel gene CLCN1, where fetal exon inclusion causes myotonia by reducing chloride conductance, and the insulin receptor gene INSR, where exon 11 skipping promotes insulin resistance via production of the short isoform.^[34] Other affected targets encompass cardiac sodium channel SCN5A, whose neonatal exon retention slows conduction and contributes to arrhythmias, and muscle calcium release channel RYR1, where isoform shifts disrupt excitation-contraction coupling.^[35] These splicing aberrations are exacerbated by upregulation of the RNA-binding protein CUGBP1 in DM1, which antagonizes MBNL and further deregulates targets like cardiac troponin T (TNNT2).^[9] Nuclear foci formation not only traps MBNL but also other splicing factors, amplifying the transcriptome-wide dysregulation observed in patient-derived cells and animal models.^[36] Secondary contributions to pathogenesis include haploinsufficiency of the host genes DMPK in DM1 and CNBP in DM2, arising from repeat-mediated transcriptional silencing or instability of the mutant allele. DMPK reduction affects protein kinase signaling in muscle and heart, while CNBP loss impairs zinc finger-mediated RNA chaperone functions, potentially compounding RNA toxicity in early disease stages.^[37] Additionally, altered microRNA expression, such as downregulation of miR-206 in DM1 skeletal muscle, disrupts pathways involved in myogenesis and regeneration, contributing to progressive muscle weakness.^[11] Furthermore, emerging evidence indicates that the toxic RNA expansions can induce cellular senescence in affected cells, exacerbating progressive tissue dysfunction through mechanisms like reduced proliferative capacity and chronic inflammation.^[38] DM1 generally manifests greater severity than DM2, attributable to the location of the repeat expansion in the DMPK 3' untranslated region (enhancing RNA toxicity), greater efficiency of MBNL sequestration by CUG repeats compared to CCUG repeats, and its pronounced impact on embryonic development in congenital cases.^[28] Despite these differences, shared pathways like SCN5A and RYR1 mis-splicing underlie overlapping cardiac and skeletal muscle phenotypes, with MBNL1/2 loss-of-function models confirming their mechanistic convergence.^[31] Emerging evidence implicates repeat-associated non-AUG (RAN) translation of the expanded RNAs, generating homopolymeric toxic peptides (e.g., polyglutamine or polyarginine in all reading frames) that aggregate and exacerbate cellular toxicity independent of RNA foci.^[39] These peptides, detected in DM patient tissues, represent a complementary gain-of-function mechanism, as demonstrated in Drosophila and mouse models where RAN products induce neurodegeneration and muscle defects.^[40]

Histological and Tissue Changes

In myotonic dystrophy type 1 (DM1), muscle biopsies characteristically reveal a dystrophic pattern without significant necrosis or inflammatory infiltrates, featuring selective atrophy of type 1 muscle fibers, rows of centralized or internalized nuclei in up to 80-95% of fibers, ring fibers (also known as ringbinden fibers), and sarcoplasmic masses consisting of hyalinized eosinophilic material devoid of myofibrils.^[1]^[41]^[42] In contrast, myotonic dystrophy type 2 (DM2) shows milder histological changes, including type 2 fiber atrophy, increased internal nuclei, and fiber size variation, but with fewer ring fibers and sarcoplasmic masses compared to DM1.^[2]^[43] Cardiac tissue in DM1 exhibits progressive fibrosis and fatty replacement, particularly affecting the conduction system, including the sinoatrial node, atrioventricular node, and His-Purkinje fibers, which contributes to arrhythmias and conduction abnormalities.^[44]^[45] These fibrofatty changes are observed in both atrial and ventricular myocardium, with interstitial fibrosis predominating in the latter.^[46] Central nervous system pathology in DM1 includes white matter lesions characterized by myelin loss, gliosis, and axonal degeneration, often in periventricular and deep white matter regions, alongside ventricular dilation indicative of brain atrophy.^[47]^[48] Neuronal loss is evident in brainstem nuclei, such as the pontine locus coeruleus and medullary olivary nuclei, correlating with cognitive and autonomic impairments.^[49] In the lens, epithelial cell changes in DM1 involve reduced cell density and morphological abnormalities, such as irregular cell shapes and decreased proliferation, leading to posterior subcapsular opacities.^[50] Gonadal tissues show atrophy with fibrosis; in males, this manifests as loss of seminiferous tubules and interstitial fibrosis in the testes, resulting in primary hypogonadism.^[6] Muscle atrophy in DM1 preferentially affects distal muscles early in the disease, such as those in the hands and feet, progressing to proximal involvement later, whereas DM2 primarily involves proximal and axial muscles from onset.^[51]^[2] With the advent of genetic testing, muscle biopsy utility for diagnosis has declined, though it remains valuable for confirming histopathological features in atypical cases.^[1] Magnetic resonance imaging (MRI) of muscles in DM1 demonstrates progressive fatty infiltration, particularly in the lower extremities and trunk, with fat fraction increases correlating to disease duration and severity, often exceeding 70% in affected regions.^[52]^[53]

Diagnosis

Clinical Evaluation and Classification

Clinical evaluation of myotonic dystrophy begins with a thorough medical history and physical examination to identify characteristic features such as muscle weakness, myotonia, and multisystem involvement, often prompted by a family history of similar symptoms.^[54] The hallmark clinical sign is myotonia, demonstrated by delayed muscle relaxation after contraction, which can be elicited through grip release testing or percussion of thenar muscles during the exam.^[55] Additional initial assessments include evaluation for facial weakness, ptosis, and temporal wasting, as well as slit-lamp examination to detect early posterior subcapsular cataracts, which are common in affected individuals.^[1] Diagnostic criteria for myotonic dystrophy typically require a combination of clinical myotonia (observed or via electromyography), progressive muscle weakness, and a positive family history, as outlined in guidelines from the Muscular Dystrophy Association and consensus recommendations.^[54]^[22] These criteria help establish a presumptive diagnosis prior to genetic confirmation, emphasizing the need for multidisciplinary input to assess associated features like cognitive or cardiac symptoms.^[6] Classification distinguishes between type 1 (DM1) and type 2 (DM2) myotonic dystrophy based on clinical presentation, with DM1 featuring prominent distal muscle weakness, early facial diplegia, and frequent cataracts, while DM2 shows primarily proximal weakness, reduced myotonia, and more prominent muscle pain or stiffness.^[6]^[56] In DM1, weakness often starts in the hands and face, progressing to ankle dorsiflexors, whereas DM2 affects hip and shoulder girdle muscles more severely, with less severe overall myotonia and later-onset cataracts.^[57] For DM1, further categorization occurs by age of onset, influencing prognosis and management: congenital form presents at birth or within the first three months with severe hypotonia, respiratory distress, and facial weakness; childhood onset (ages 1-14 years) involves developmental delays, behavioral issues, and mild weakness; adult onset (ages 15-40 years) manifests as classic progressive weakness and myotonia; and late-onset (after 40 years) is milder with primarily cataracts and minimal weakness.^[1]^[21] Severity in DM1 is often assessed using the Muscular Impairment Rating Scale (MIRS), a five-stage tool that evaluates overall muscular involvement from no weakness (stage 1) to severe generalized weakness with dependency (stage 5), providing a reliable measure of disease progression.^[58] This scale correlates with functional status and is widely used in clinical trials to monitor impairment without requiring extensive testing.^[59]

Genetic Testing Methods

Genetic testing for myotonic dystrophy type 1 (DM1) typically involves polymerase chain reaction (PCR) to detect small CTG repeat expansions in the DMPK gene, while larger expansions require triplet repeat-primed PCR (TP-PCR) or Southern blot analysis to accurately size the repeats, as these methods can identify expansions up to thousands of CTG units.00078-9/fulltext)^[1] For myotonic dystrophy type 2 (DM2), testing targets the CCTG repeat expansion in intron 1 of the CNBP gene, commonly using repeat-primed PCR combined with Southern blot to detect and size the complex repeats, which can exceed 10,000 base pairs.^[2]^[60] Prenatal testing for at-risk pregnancies is performed via chorionic villus sampling (CVS) at 10-12 weeks gestation or amniocentesis at 15-18 weeks, allowing direct analysis of fetal DNA for pathogenic repeat expansions in either DM1 or DM2 using the same molecular methods as diagnostic testing.^[1]^[2] Non-invasive prenatal options, such as cell-free fetal DNA analysis, are emerging for monogenic disorders but remain limited for repeat expansion disorders like myotonic dystrophy due to technical challenges in accurately sizing large repeats.^[61] Predictive testing for asymptomatic at-risk individuals, including adults and children, follows a structured protocol that includes pre- and post-test genetic counseling to address psychological implications; it often employs a two-step approach starting with PCR to identify normal or small expansions, followed by confirmatory TP-PCR or Southern blot if results are borderline or suggestive of intermediate alleles.^[1]00078-9/fulltext) This testing is recommended for family members of confirmed cases to determine carrier status and inform reproductive planning.^[2] These genetic tests exhibit near 100% sensitivity and specificity for detecting pathogenic repeat expansions in both DM1 and DM2 when performed in accredited laboratories, though DM2 testing faces challenges from repeat interruptions (such as TCTG or other motifs within the CCTG tract) that can complicate sizing and interpretation, sometimes requiring advanced methods like long-read sequencing for precise characterization.^[62]^[27] The American College of Medical Genetics and Genomics (ACMG) provides technical standards for DM1 testing, recommending molecular confirmation in probands with suggestive symptoms and offering family testing for at-risk relatives, with updates emphasizing the use of TP-PCR as a first-line method for its efficiency in detecting large expansions; similar principles apply to DM2 under broader ACMG guidelines for repeat expansion disorders.00078-9/fulltext)^[63]

Supportive Diagnostic Tests

Electromyography (EMG) is a key supportive test in evaluating myotonic dystrophy, demonstrating characteristic myotonic discharges with waxing and waning amplitude and frequency, often described as a "dive bomber" sound, which helps confirm myotonia and differentiate from other myopathies.^[6] These electrical myotonic potentials are typically more prominent in distal muscles in DM1 and may show waning patterns in DM2, aiding in subtype distinction when clinical features are equivocal.^[64] Muscle biopsy, though rarely performed due to the availability of genetic testing, can reveal dystrophic changes such as fiber size variation, internalized nuclei, ring fibers, and sarcoplasmic masses in atypical or undiagnosed cases.^[1] Histological findings are similar between DM1 and DM2, supporting a presumptive diagnosis of myotonic dystrophy but not confirming the specific subtype without molecular analysis.^[23] Cardiac evaluation is essential given the high prevalence of conduction abnormalities; electrocardiography (ECG) detects prolonged PR intervals, bundle branch blocks, and atrial fibrillation in up to 80% of adults with DM1.^[65] Ambulatory Holter monitoring identifies ventricular arrhythmias and higher-degree atrioventricular blocks, which may be asymptomatic and require intervention, while echocardiography assesses for left ventricular dysfunction or cardiomyopathy, present in about 10-20% of cases.^[66]^[67] Respiratory function tests, including pulmonary function tests (PFTs), typically show a restrictive pattern due to diaphragmatic and intercostal muscle weakness, with reduced forced vital capacity (FVC) in supine position indicating diaphragmatic involvement.^[68] Sleep studies, such as polysomnography, reveal central and obstructive sleep apnea or nocturnal hypoventilation, affecting over 50% of patients and correlating with daytime respiratory symptoms.^[69] Serum creatine kinase (CK) levels are mildly elevated in symptomatic patients, often 2-5 times the upper limit of normal, reflecting muscle damage but not specific to myotonic dystrophy.^[1] Endocrine assessments, including oral glucose tolerance tests, uncover insulin resistance and impaired glucose metabolism in approximately 5-17% of DM1 cases and 25-75% of DM2 cases, alongside thyroid function tests for subclinical hypothyroidism.^[70]^[2] Neuroimaging, particularly brain MRI, demonstrates white matter hyperintensities, cortical atrophy, and ventricular enlargement, supporting central nervous system involvement and correlating with cognitive impairment.^[71] These tests collectively aid in phenotyping, monitoring disease progression, and identifying complications in equivocal cases, complementing clinical and genetic evaluations without serving as primary diagnostic tools.^[6]

Management

Symptomatic Treatments

Symptomatic treatments for myotonic dystrophy primarily target core manifestations such as myotonia, cardiac conduction abnormalities, respiratory insufficiency, endocrine disruptions, and ocular complications, using pharmacological and procedural interventions to alleviate symptoms without addressing the underlying genetic defect.^[72]^[73] Management of myotonia, the delayed muscle relaxation after contraction, focuses on sodium channel blockers to reduce muscle stiffness and improve daily function. Mexiletine, a class Ib antiarrhythmic agent, is the most evidence-based option, administered at doses of 150 to 200 mg three times daily; it has been shown in randomized controlled trials to significantly reduce handgrip myotonia duration and subjective stiffness scores in patients with myotonic dystrophy type 1 (DM1), with improvements observed in up to 40% of cases over short-term use and sustained benefits in longer trials without major adverse effects beyond mild gastrointestinal upset.^[74]^[75] Although FDA-approved for nondystrophic myotonias, mexiletine is commonly used off-label for myotonic dystrophy due to its efficacy and tolerability profile.^[76] Alternative agents include phenytoin (typically 300 mg daily) and carbamazepine, which have demonstrated myotonia relief in smaller studies but carry higher risks of cardiac side effects, such as ventricular tachycardia, particularly in patients with preexisting conduction issues.^[73]^[77] Cardiac involvement in myotonic dystrophy, including atrioventricular (AV) block and arrhythmias, requires proactive monitoring and intervention to prevent sudden death. Implantation of a permanent pacemaker is recommended for marked first-degree AV block with a PR interval exceeding 240 ms, as this threshold correlates with progression to higher-degree blocks in DM1 patients, based on consensus guidelines from cardiology experts.^[78]^[79] For supraventricular tachycardia, beta-blockers such as metoprolol may be used cautiously in patients without significant AV conduction delays or after pacemaker placement, with gradual titration to avoid exacerbating fatigue or bradycardia.^[80] Certain anesthetics, including succinylcholine and volatile agents like halothane, should be avoided during procedures due to risks of exaggerated myotonic responses, hyperkalemia, and prolonged respiratory depression.^[81]^[82] Respiratory symptoms, such as nocturnal hypoventilation from diaphragmatic weakness, are addressed with noninvasive ventilation to maintain airway patency and gas exchange. Bilevel positive airway pressure (BiPAP) therapy, often initiated when vital capacity falls below 50% predicted or with symptoms like daytime somnolence, has been shown to improve sleep quality, reduce hypoventilation episodes, and slow pulmonary function decline in neuromuscular disorders including myotonic dystrophy.^[83]^[84] Mechanically assisted cough devices, using insufflation-exsufflation cycles, are recommended for patients with weak cough efficacy (peak cough flow <270 L/min) to clear secretions and prevent recurrent infections.^[85]^[86] Endocrine abnormalities, prevalent in up to 30% of patients, include insulin resistance and hypogonadism, which contribute to metabolic and reproductive challenges. Metformin, at low doses starting from 500 mg daily, is the preferred initial therapy for insulin resistance and diabetes in myotonic dystrophy, as it enhances insulin sensitivity, reverses cellular metabolic defects in patient-derived fibroblasts, and improves glycemic control without worsening myotonia.^[4]^[87] For hypogonadism, characterized by low testosterone and impaired gonadal function, hormone replacement with testosterone or estrogen-progesterone regimens is indicated to mitigate symptoms like fatigue and osteoporosis, following standard endocrinologic protocols adjusted for individual comorbidities.^[88] Ocular manifestations, particularly posterior subcapsular cataracts affecting over 90% of adult patients, are managed surgically once visual acuity declines below 20/40. Cataract extraction via phacoemulsification with intraocular lens implantation is safe and effective, yielding significant visual improvement, though preoperative assessment for ptosis and myotonia is essential to optimize outcomes.^[89] Miotics, such as pilocarpine, should be avoided in glaucoma management due to potential exacerbation of miosis-related complications during or after surgery in this population.^[90]

Rehabilitative Interventions

Rehabilitative interventions in myotonic dystrophy focus on preserving mobility, preventing complications such as contractures, and enhancing daily function through targeted physical and supportive strategies. These approaches are essential due to the progressive muscle weakness and myotonia characteristic of the condition, particularly in myotonic dystrophy type 1 (DM1) and type 2 (DM2). Interventions are individualized based on disease type, severity, and patient symptoms, with close monitoring for fatigue to avoid exacerbation of weakness.^[91] Physical therapy plays a central role, emphasizing low-intensity aerobic exercises to maintain joint range of motion and prevent contractures while minimizing the risk of overexertion, which can worsen myotonia. Guidelines recommend moderate-intensity programs, such as cycling three times per week for 20-30 minutes, which have been shown to improve endurance and cardiovascular fitness without inducing excessive fatigue in patients with DM1. Resistance training with light weights or resistance bands is also encouraged to counteract muscle atrophy, starting at low loads and progressing gradually under supervision. Therapists assess gait, balance, and posture regularly to adapt exercises, incorporating stretching to address stiffness.^[22]^[92]^[93] Orthotic devices provide critical support for weakened limbs, helping to stabilize joints and improve gait efficiency. Ankle-foot orthoses (AFOs) are commonly prescribed to address foot drop in DM1, reducing the risk of falls and trips by supporting dorsiflexion during walking; custom-fitted AFOs have demonstrated improvements in gait speed and energy expenditure. Wrist splints or hand orthoses assist with grip strength and fine motor tasks, preventing ulnar deviation and enhancing activities like writing or eating. These devices are fitted early in disease progression and adjusted as muscle wasting advances.^[94]^[95]^[96] As weakness progresses, mobility aids such as canes, walkers, or powered wheelchairs become necessary to maintain independence and reduce fall risk. Adaptive equipment for activities of daily living, including button hooks, reachers, and raised toilet seats, further supports self-care by compensating for reduced dexterity and strength. Selection of aids is guided by functional assessments, ensuring they align with the patient's lifestyle and home environment.^[94]^[96] Speech and swallow therapy is particularly relevant for DM1 patients experiencing dysphagia, which affects up to 60% and increases aspiration risk. Therapists employ techniques such as chin-tuck positioning, thickened liquids, and oropharyngeal exercises to improve swallowing safety and efficiency. Respiratory muscle training, including inspiratory muscle exercises, helps strengthen diaphragmatic function and prevent respiratory complications in advanced stages. These interventions are delivered by speech-language pathologists, with videofluoroscopic swallow studies informing personalized plans.^[97]^[98] Pain management in rehabilitation prioritizes non-opioid strategies to address myotonia-related cramps and joint discomfort. Transcutaneous electrical nerve stimulation (TENS) units are used to alleviate muscle cramps by modulating nerve signals, providing relief during episodes without promoting dependency. Non-opioid analgesics like acetaminophen are integrated as needed, alongside physical therapy modalities such as warm compresses or gentle massage to reduce myalgia. Overall, rehabilitative care is coordinated to monitor fatigue thresholds and adjust interventions, ensuring long-term quality of life benefits.^[99]^[100]^[91]

Multidisciplinary Care

Management of myotonic dystrophy (DM) requires a coordinated multidisciplinary approach to address its multisystem involvement, including muscular, cardiac, respiratory, endocrine, cognitive, and psychosocial aspects. This team-based care model ensures comprehensive monitoring, timely interventions, and support for patients and families, leading to optimized outcomes.^[22] The core multidisciplinary team typically includes a neurologist to oversee overall coordination, a cardiologist for cardiac surveillance, a pulmonologist for respiratory assessment, an endocrinologist for metabolic issues such as diabetes and hypothyroidism, a psychologist for cognitive and behavioral support, and a genetic counselor for family planning and inheritance risks. Additional specialists, such as ophthalmologists, otolaryngologists, and therapists, may be involved as needed based on individual symptoms. This composition facilitates integrated care, with regular team meetings to review patient progress and adjust plans.^[101]^[22] Genetic counseling is essential for all patients with DM type 1 (DM1) and their families, particularly regarding preconception risks. As an autosomal dominant disorder, each child of an affected individual has a 50% chance of inheritance, with anticipation leading to more severe symptoms and earlier onset in successive generations, especially when transmitted by the mother. Counselors discuss options such as preimplantation genetic diagnosis (PGD) combined with in vitro fertilization (IVF) to select unaffected embryos, prenatal testing via amniocentesis or chorionic villus sampling, and adoption or childlessness as alternatives. Early counseling empowers informed reproductive decisions and mitigates intergenerational transmission.^[102]^[103]^[22] Psychosocial support addresses the cognitive impairments common in DM1, such as executive dysfunction, apathy, and avoidant personality traits, which can affect daily functioning and relationships. Interventions include psychological therapy to manage these issues, family counseling to navigate dynamics altered by progressive disability and inheritance concerns, and peer support groups for emotional coping. Participation in patient registries, like the Myotonic Dystrophy Family Registry, not only facilitates research recruitment but also provides community resources and advocacy, enhancing long-term psychosocial well-being.^[104]^[105]^[106] Standardized monitoring protocols are integral to proactive management, with annual electrocardiograms (ECGs) recommended for all DM1 patients to detect conduction abnormalities, and echocardiography every 1-3 years or as indicated for structural heart disease. Respiratory function tests, including forced vital capacity and peak cough flow, should be performed annually or biannually if abnormalities are present to identify early insufficiency. For pediatric patients transitioning to adult care, structured handoffs around age 18-21 ensure continuity, involving joint clinics to address evolving needs.^[72]^[22]^[107] In advanced DM1, palliative care focuses on advance care planning for potential respiratory failure, the leading cause of mortality, including discussions on non-invasive ventilation preferences, do-not-intubate orders, and symptom management for dyspnea and fatigue. Integration of palliative services early in the disease course improves quality of life by aligning treatments with patient goals and providing holistic end-of-life support.^[108]^[22] Multidisciplinary care has significantly improved survival in DM1 compared to historical cohorts, with median age at death increasing from approximately 48 years in earlier studies to 55-60 years in recent populations, attributed to better cardiac pacing, respiratory support, and overall coordination; this represents an extension of 10-20 years in life expectancy for many patients. Such approaches also enhance quality of life by reducing complications and supporting independence.^[109]^[110]^[22]

Prognosis and Epidemiology

Prognostic Factors

In myotonic dystrophy type 1 (DM1), the congenital form is associated with a neonatal mortality rate of 20-40%, primarily due to respiratory failure from severe hypotonia and weakness.^[111]^[19] For individuals with adult-onset DM1, median survival is typically 55-60 years, with progressive muscle weakness, respiratory complications, and cardiac issues limiting life expectancy.^[110]^[112]^[113] In contrast, myotonic dystrophy type 2 (DM2) generally follows a milder course, with median survival of approximately 71 years, reduced compared to the general population (78-82 years), though still longer than in DM1.^[114] The primary prognostic concerns in DM2 involve metabolic complications such as insulin resistance and diabetes, alongside increasing disability that often becomes prominent in the 40s and 50s, leading to reduced mobility and higher pain interference.^[2]^[115] Key modifiers of prognosis in both forms include the length of the nucleotide repeat expansion, where longer repeats correlate with earlier onset, greater severity, and worse outcomes, such as heightened cardiac risk in DM1 with expansions over 1,300 CTG repeats.^[116]^[117] Early interventions like pacemaker implantation for conduction defects can significantly extend survival in DM1 by mitigating arrhythmia-related sudden death.^[1] Lifestyle factors, including regular aerobic exercise and healthy diet, may delay functional decline and improve metabolic management, though evidence remains preliminary.^[118]^[65] Respiratory and cardiac complications dominate mortality in DM1, with pneumonia and aspiration events alongside arrhythmias accounting for over 50% of deaths, often occurring in the fifth or sixth decade.^[112]^[110]^[113] Progressive disability and cognitive decline substantially impair quality of life across both DM types, reducing independence through worsening muscle weakness, executive function deficits, and psychosocial challenges that emerge over decades.^[119]^[120]^[121]

Population Distribution

Myotonic dystrophy type 1 (DM1) has a worldwide prevalence of approximately 9.3 per 100,000 individuals (1 in 10,800), while type 2 (DM2) is estimated at 2.3 per 100,000 (1 in 43,500), based on a 2022 systematic review; these figures reflect the most common adult-onset muscular dystrophy, with DM1 being more frequent overall, though estimates vary widely due to underdiagnosis.^[122] Incidence for DM1 is estimated around 5-10 per 100,000 live births, though this is likely an underestimate due to underdiagnosis of mild, late-onset cases that may go unrecognized until adulthood.^[1] Improved genetic screening has helped identify more cases, but many remain undetected, particularly in populations with limited access to testing.^[122] Geographic variations are pronounced, often linked to founder effects. In the Saguenay–Lac-Saint-Jean region of Quebec, Canada, DM1 prevalence reaches 1 in 550 due to a historical founder mutation event among French Canadian settlers.^[123] Prevalence is higher in European populations, estimated at up to 20 per 100,000 in some areas like France and an average of 12.25 per 100,000 across Europe, compared to lower rates elsewhere.^[124] DM2 shows a stronger association with Northern European ancestry, where its prevalence approaches that of DM1 in some areas, such as Germany and Finland.^[125] The condition is rarer among non-European ethnic groups, with low or absent cases reported in Asian and sub-Saharan African populations, possibly due to haplotype differences limiting expansion of the causative repeats.^[126]^[127] Demographically, myotonic dystrophy affects males and females equally, with no significant sex-based prevalence disparity. However, congenital DM1 exhibits a strong maternal transmission bias, occurring almost exclusively when inherited from the mother due to greater CTG repeat expansion during female gametogenesis.^[1] In aging populations, detection rates have increased as late-onset mild cases become apparent with advancing age. Overall trends remain stable globally, bolstered by advances in genetic diagnosis that enhance identification, though socioeconomic factors continue to influence access to care and outcomes in underserved regions.^[122]

History and Research

Historical Context

The earliest descriptions of myotonic dystrophy emerged in the late 19th and early 20th centuries, initially recognized as a form of paramyotonia or myotonia with atrophy. In 1902, Russian neurologist Grigory Rossolimo reported a case of "myotonie atrophique," highlighting muscle stiffness and wasting, which laid groundwork for identifying the condition as distinct from simple myotonia congenita.^[128] This was followed by German physician Hans Steinert's seminal 1909 publication, where he coined the term "dystrophia myotonica" to describe the multisystemic nature of the disorder in six patients, emphasizing progressive muscle weakness, myotonia, and associated cataracts and gonadal atrophy.^[13] Steinert's work established myotonic dystrophy type 1 (DM1) as a recognized entity, distinguishing it from other myotonic disorders.^[129] In the mid-20th century, research advanced understanding of its inheritance and clinical variability. Heinrich Curschmann, in the 1910s, further elucidated the systemic features, including cardiac involvement and endocrine disturbances, expanding recognition beyond skeletal muscle pathology.^[6] By 1975, Peter Harper identified the phenomenon of anticipation, where symptoms worsened and onset occurred earlier in successive generations, a key insight into the disorder's dynamic genetics.^[130] Linkage studies in the 1980s mapped the DM1 locus to chromosome 19, with tight association to markers like apolipoprotein C2 confirmed by 1986, enabling presymptomatic testing and family counseling.^[131] These efforts shifted diagnostic approaches from reliance on electromyography and muscle biopsy toward genetic analysis. The discovery of myotonic dystrophy type 2 (DM2) in the 1990s marked a major expansion of the disease spectrum. Initially termed proximal myotonic myopathy (PROMM) by Karl Ricker and colleagues in 1994, DM2 was recognized as a distinct entity characterized by proximal weakness and milder myotonia, linked to chromosome 3 rather than 19.^[132] The underlying mutation—a CCTG tetranucleotide repeat expansion in the CNBP gene—was identified in 2001, confirming DM2's molecular basis and its RNA-mediated pathogenesis similar to DM1. Key milestones included the 1992 identification of the CTG repeat expansion in the DMPK gene for DM1, enabling the first direct genetic tests and transitioning diagnosis from histopathological to molecular methods. In the 1990s, international patient registries, such as those initiated by the Myotonic Dystrophy Foundation, were established to facilitate collaborative research and natural history studies.^[133]

Current and Emerging Research

Current research in myotonic dystrophy (DM) focuses on addressing the underlying RNA toxicity caused by nucleotide repeat expansions, with therapeutic targets centered on reducing toxic RNA foci and correcting splicing defects. Antisense oligonucleotides (ASOs) represent a primary approach, designed to bind and degrade mutant DMPK mRNA in DM1 or CNBP mRNA in DM2, thereby alleviating sequestration of RNA-binding proteins like MBNL1. For instance, delpacibart etedesiran (del-desiran, AOC 1001), an antibody-oligonucleotide conjugate from Avidity Biosciences, targets DMPK mRNA and has demonstrated reductions in RNA foci in preclinical models and improved muscle strength in phase 1/2 trials. Similarly, DYNE-101 from Dyne Therapeutics, another ASO targeting DMPK, showed symptom reduction and functional improvements after intravenous infusions every 8 weeks in early clinical testing; additional one-year data from the phase 1/2 ACHIEVE trial were reported in October 2025, demonstrating sustained improvements. Gene editing strategies, such as CRISPR/Cas9, aim to excise expanded CTG repeats in the DMPK gene; preclinical studies in mouse models have achieved muscle-specific editing, reversing molecular defects and improving phenotypic outcomes like grip strength. Vertex Pharmaceuticals, in collaboration with CRISPR Therapeutics, is advancing in vivo gene-editing therapies for DM1, with investigational programs targeting repeat expansions. Ongoing clinical trials emphasize disease-modifying potential beyond symptomatic relief. The phase 3 HARBOR trial (NCT06411288) for del-desiran enrolled over 150 adults with DM1, with enrollment completed in July 2025; it evaluates video hand opening time as the primary endpoint for myotonia and function, with topline data expected in late 2026. Sanofi's SAR446268, an AAV-based gene therapy, received FDA Fast Track designation in September 2025 for non-congenital DM1, focusing on delivering corrective genes to muscle tissue in phase 1/2 studies, with first patient enrollment planned for late 2025. Earlier trials, such as the phase 1/2 ACHIEVE for DYNE-101, confirmed safety and spliceopathy corrections via muscle biopsies. For myotonia, while mexiletine was validated in 2010s studies like the RIFAMA trial (NCT01406873) showing improved 6-minute walk distance over 6 months, studies highlight the need for alternatives due to potential cardiac risks. Stem cell approaches remain preclinical, with induced pluripotent stem cells (iPSCs) used to model DM1 muscle regeneration and test therapies, though no active trials were reported in 2025. Key research areas include identifying biomarkers for disease progression to facilitate trial endpoints. Muscleblind-like 1 (MBNL1) protein levels and RNA splicing patterns serve as sensitive indicators of RNA toxicity, with quantitative assays like ddPCR enabling monitoring in blood and muscle. The END-DM1 natural history study (NCT03981575), enrolling approximately 700 adults across 15 sites, tracks progression via MRI, biofluids, and functional measures to validate biomarkers like white matter integrity for CNS involvement; participant recruitment was completed by Q3 2025. Cognitive research explores therapies targeting brain splicing defects, with ASOs showing promise in preclinical models for alleviating deficits in executive function. For DM2, investigations emphasize metabolic links, such as insulin resistance and type 2 diabetes comorbidity, with underfunded studies probing CNBP-related pathways for targeted interventions. Organizations like the Myotonic Dystrophy Foundation (MDF) coordinate global efforts, maintaining a drug development pipeline tracking over 20 candidates and supporting the Myotonic Dystrophy Family Registry for trial recruitment. The TREAT-NMD network provides standardized datasets for DM1 clinical trials, aiding endpoint harmonization since 2009. Natural history cohorts like END-DM1, backed by Dyne Therapeutics, inform trial design by quantifying variability in adult DM1 progression. Despite advances, significant gaps persist: no approved disease-modifying treatments exist for DM as of 2025, with care limited to symptom management. DM2 research lags due to lower prevalence and funding, lacking dedicated trials compared to DM1. Pediatric interventions are underdeveloped, with most studies excluding congenital cases, and broader needs include diverse population representation in trials to address ethnic variability in repeat expansions.

References

[1]
Myotonic Dystrophy Type 1 - GeneReviews® - NCBI Bookshelf
Myotonic dystrophy type 1 (DM1) is a multisystem disorder that affects skeletal and smooth muscle as well as the eye, heart, endocrine system, and central ...
[2]
Myotonic Dystrophy - StatPearls - NCBI Bookshelf
Jun 26, 2023 · Myotonic dystrophy (DM) is considered a subgroup of myopathy and the most common type of muscular dystrophy that begins in adulthood.
[3]
Myotonic Dystrophy Type 2 - GeneReviews® - NCBI Bookshelf
Sep 21, 2006 · Myotonic dystrophy type 2 (DM2) is characterized by myotonia and muscle dysfunction (proximal and axial weakness, myalgia, and stiffness)<|control11|><|separator|>
[4]
Myotonic Dystrophies: A Genetic Overview - PubMed
Feb 17, 2022 · There are two genetically distinct types of myotonic dystrophy: myotonic dystrophy type 1 (DM1) and myotonic dystrophy type 2 (DM2), both dominantly inherited.
[5]
Myotonic Dystrophies: A Genetic Overview - PMC - PubMed Central
Myotonic dystrophies (DM) are the most common muscular dystrophies in adults, which can affect other non-skeletal muscle organs such as the heart, brain and ...
[6]
The myotonic dystrophy experience: a North American cross ...
Myotonic dystrophy (DM) is a multisystemic condition known primarily for muscle weakness, muscle atrophy, and myotonia, along with early cataracts, cardiac ...
[7]
Myotonic dystrophy | About the Disease | GARD
Myotonic dystrophy is a disease that affects the muscles and other body systems. It is the most common form of muscular dystrophy that begins in adulthood.
[8]
Myotonic Dystrophy: RNA Pathogenesis Comes into Focus - PMC
We discuss the pathogenic mechanisms that have been proposed for the myotonic dystrophies, the clinical and molecular features of DM1 and DM2,
[9]
Pathogenic mechanisms of myotonic dystrophy - PMC
The RNA results in a toxic effect through two RNA-binding proteins: MBNL1 (muscleblind-like 1) and CUGBP1 (CUG-binding protein 1). In DM1, MBNL1 is sequestered ...Evidence Of Rna... · Mbnl1 · Cugbp1
[10]
Myotonic dystrophy: MedlinePlus Genetics
Jul 1, 2020 · Myotonic dystrophy is characterized by progressive muscle wasting and weakness. People with this disorder often have prolonged muscle contractions (myotonia)
[11]
Myotonic dystrophy type 2: the 2020 update - PMC - PubMed Central
Myotonic dystrophy type 2 results from an unstable tetranucleotide repeat expansion, CCTG in intron 1 of the nucleic acid-binding protein (CNBP) gene ( ...
[12]
“Dystrophia Myotonica” and the Legacy of Hans Gustav Wilhelm ...
DM type 1 (DM1) is a commonly inherited adult muscle disorder. In 1909, its characteristics were first described by Hans Steinert (1875–1911), a German ...
[13]
Myotonic dystrophy type 2 caused by a CCTG expansion in intron 1 ...
We now report that DM2 is caused by a CCTG expansion (mean approximately 5000 repeats) located in intron 1 of the zinc finger protein 9 (ZNF9) gene.
[14]
Clinical aspects, molecular pathomechanisms and management of ...
Myotonic dystrophy (DM) is the most common adult muscular dystrophy, characterized by autosomal dominant progressive myopathy, myotonia and multiorgan ...
[15]
Myotonic Dystrophy: Disease Repeat Range, Penetrance, Age of ...
Feb 14, 2017 · Myotonic dystrophy (DM) is an autosomal dominant neuromuscular disease primarily characterized by myotonia and progressive muscle weakness.
[16]
Signs and Symptoms of Congenital DM1 - Myotonic Dystrophy (DM)
They appear floppy, have trouble breathing, and suck and swallow poorly. In the past, many infants with congenital DM did not survive. Today, with special care ...Missing: manifestations | Show results with:manifestations
[17]
Congenital and childhood myotonic dystrophy - PubMed Central - NIH
In neonates and children, DM1 predominantly affects muscle strength, cognition, respiratory, central nervous and gastrointestinal systems. Sleep disorders are ...
[18]
Signs and Symptoms of Childhood-Onset DM1 - Myotonic Dystrophy ...
The first symptoms tend to be more behavioral and cognitive than physical. Intellectual impairment with low IQ is a common manifestation. Some people with ...
[19]
Signs and Symptoms of Adult-Onset DM1 and DM2 - Myotonic ...
The mild form of DM1 is characterized by mild weakness, myotonia, and cataracts. Age at onset is between 20 and 70 years (typically onset occurs after age 40), ...
[20]
Consensus-based care recommendations for adults with myotonic ...
DM1 is a multisystem and heterogeneous disease characterized by distal weakness, atrophy, and myotonia, as well as symptoms in the heart, brain, ...
[21]
Myotonic Dystrophy Type 2: An Update on Clinical Aspects, Genetic ...
Myotonic dystrophies (DMs) represent a group of dominantly inherited, multisystemic diseases that share the core features of myotonia, muscle weakness, muscular ...
[22]
Entry - #160900 - MYOTONIC DYSTROPHY 1; DM1 - (OMIM.ORG)
The disorder shows genetic anticipation, with expansion of the repeat number dependent on the sex of the transmitting parent. Alleles of 40 to 80 repeats are ...
[23]
Myotonic dystrophy type 1 testing, 2024 revision: A technical ...
Ranges of DMPK CTG repeats are as follows: normal alleles (∼5 to 34 CTG ... CTG repeats, and genetic anticipation. Additionally, variant repeats with ...
[24]
Characterization of full-length CNBP expanded alleles in myotonic ...
Aug 26, 2022 · Myotonic dystrophy type 2 (DM2) is caused by CCTG repeat expansions in the CNBP gene, comprising 75 to >11,000 units and featuring extensive ...
[25]
Review Myotonic dystrophy: Emerging mechanisms for DM1 and DM2
It has an autosomal dominant mode of inheritance and disease severity generally correlates with repeat length. The first insight into the molecular ...
[26]
Myotonic Dystrophy - PMC - PubMed Central
Both disorders have autosomal dominant inheritance and multisystem features ... Accordingly, there is less anticipation in DM2 than in DM1.
[27]
Myotonic Dystrophies: A Genetic Overview - MDPI
There are two genetically distinct types of myotonic dystrophy: myotonic dystrophy type 1 (DM1) and myotonic dystrophy type 2 (DM2), both dominantly inherited.
[28]
Genotype-Phenotype Correlations and Characterization ... - Frontiers
Jun 25, 2020 · Typically, DM2 is milder and has a later age of onset than DM1. Additionally, repeat length is not correlated with severity of symptoms or age ...
[29]
MBNL Sequestration by Toxic RNAs and RNA Mis-Processing ... - NIH
SUMMARY. For some neurological disorders, disease is primarily RNA-mediated due to expression of non-coding microsatellite expansion RNAs (RNAexp). Toxicity ...
[30]
Deciphering the Complex Molecular Pathogenesis of Myotonic ...
Jan 27, 2022 · This model recapitulates RNA toxicity alterations by displaying myopathy, centrally located nuclei in muscle fibers, and AS defects [23]. (2) ...
[31]
Myotonic Dystrophy: From Molecular Pathogenesis to Therapeutics
Oct 8, 2022 · ... sequestration on RNA processing. CUGBP1 was identified as the ... RNA Toxicity in Myotonic Dystrophy using Small Molecules. Int. J ...
[32]
An Overview of Alternative Splicing Defects Implicated in Myotonic ...
MBNL1 and CELF1 act as antagonist regulators of several pre-mRNA targets, including cardiac troponin (cTNT), insulin receptor (INSR), chloride channel 1 (CLCN1) ...
[33]
Splicing misregulation of SCN5A contributes to cardiac-conduction ...
In conclusion, misregulation of the alternative splicing of SCN5A may contribute to a subset of the cardiac dysfunctions observed in myotonic dystrophy. Inline ...Missing: mis- | Show results with:mis-
[34]
Myotonic dystrophy RNA toxicity alters morphology, adhesion and ...
Jul 4, 2022 · To assess the toxicity of CUG RNA repeats and investigate the molecular ... toxic RNA foci, as well as MBNL protein sequestration and ...
[35]
Myotonic Dystrophy and Developmental Regulation of RNA ...
At the molecular level, DM pathogenesis is characterized by a toxic RNA gain-of-function mechanism that involves the transcription of noncoding microsatellite ...<|separator|>
[36]
Differential pathology and susceptibility to MBNL loss across ...
Despite a shared pathomechanism of MBNL sequestration in DM1 and DM2, the muscle involvement patterns are different, indicating differential muscle ...
[37]
RAN Translation Regulated by Muscleblind Proteins in Myotonic ...
LPAC and QAGR proteins are toxic to cells independent of RNA gain of function. RNA foci and nuclear sequestration of CCUG transcripts by MBNL1 is inversely ...
[38]
Myotonic dystrophy: Approach to therapy - PMC - NIH
Apr 1, 2017 · The phenomenon of repeat-associated non-ATG (RAN) translation leads to production of neurotoxic peptides (reviewed by Ranum and colleagues in ...
[39]
Myotonic dystrophy - Pathology Outlines
Aug 12, 2022 · Ring fibers and sarcoplasmic masses (dark staining regions) are frequently seen in DM1; DM1: type 1 myofiber atrophy with type 2 hypertrophy ...
[40]
Histopathological features in subsequent muscle biopsies in a ...
Dec 7, 2012 · It is characterized by fibre size variation, increased number of inner nuclei (80–95%), ring fibres and sarcoplasmic masses that lack properly ...
[41]
[PDF] Muscle pathology in myotonic dystrophy: light and electron ...
Sarcoplasmic masses, ring fibres, necrosis, and fibrosis were extremely rare ... Ring fibres were present only in one muscle bio- psy. They consisted ...
[42]
Cardiac Pathology in Myotonic Dystrophy Type 1 - PMC - NIH
Nov 2, 2021 · Of note, histological evaluation found moderate fatty infiltration of the atrial myocardium and diffuse fibrotic changes in the ventricular ...
[43]
Pathology of the cardiac conduction system in myotonic dystrophy
In 12 autopsy cases of myotonic dystrophy, the most frequently observed histopathologic lesions of the cardiac conduction system were fibrosis, fatty ...
[44]
Myotonic dystrophy: time for evidence-based therapy
Jun 16, 2014 · Pathological studies have shown that the heart in patients with DM1 is characterized by fibrosis and fatty replacement in the specialized ...
[45]
Lesion distribution and substrate of white matter damage in ...
Jan 14, 2021 · Our results suggest that white matter lesions tend to follow a similar anatomical pattern in DM1 patients, at least in the supratentorial ...
[46]
Human brain pathology in myotonic dystrophy type 1: A systematic ...
Feb 17, 2021 · Degenerative characteristics of white matter include loss of myelin in combination with a varying amount of axonal loss, dilation of ...
[47]
Cell type-specific abnormalities of central nervous system in ...
Jun 10, 2022 · Histological studies showed the CNS pathology of DM1 is characterized by myelin loss and gliosis in the deep white matter and neuronal loss in ...
[48]
Lens epithelial changes and mutated gene expression in patients ...
The lens epithelium was photographed to examine the morphological changes. mRNAs were extracted to determine myotonic dystrophy protein kinase gene expression ...Missing: histology | Show results with:histology
[49]
Myotonic Dystrophy (DM) - Diseases
the adult-onset form — begins in adolescence or young adulthood, often with weakness in the muscles of the face, neck, fingers, ...
[50]
Muscle magnetic resonance imaging in myotonic dystrophy type 1 ...
Degree of fat replacement at MRI correlated with clinical severity and disease duration, but not with CTG expansion. Fat replacement was also detected in milder ...
[51]
Quantitative magnetic resonance imaging assessment of muscle ...
Jan 10, 2023 · Other MRI studies have shown that over 70% of DM1 patients display fatty infiltration in the lower extremities, with especially severe defects ...
[52]
Diagnosis - Myotonic Dystrophy (DM) - Diseases
Muscle biopsy may suggest the diagnosis of DM in atypical cases with minimal weakness, unexplained elevations in creatine kinase, and nonspecific EMG findings.
[53]
[PDF] Consensus-based Care Recommendations for Adults with Myotonic ...
An Update Policy has been adopted for this document and will direct a systematic review of literature and appropriate follow up every three years. Myotonic ...
[54]
Myotonic Dystrophy: What It Is, Symptoms, Types & Treatment
Dec 12, 2022 · Myotonic dystrophy (DM) is an inherited multisystem condition that mainly causes progressive muscle loss, weakness and myotonia.Missing: >1000 | Show results with:>1000
[55]
Myotonic dystrophy — Knowledge Hub
An individual with DM1 has almost invariably inherited the expanded repeat from a parent with a CTG repeat number of over 34 (as new expansions of a gene with ...
[56]
Assessment of a disease-specific muscular impairment rating scale ...
The MIRS is a quick, simple, and reliable measurement of muscular impairment in DM1. The FSI questionnaire and the timed motor activities supported its ...
[57]
Assessment of a disease-specific muscular impairment rating scale ...
The MIRS is a quick, simple, and reliable measurement of muscular impairment in DM1 and is useful to monitor major stages of DM1 progression, ...
[58]
[PDF] GENETIC TESTING FOR MYOTONIC DYSTROPHY
Jul 1, 2025 · CTG repeat lengths of up to 34 are considered normal. ... understanding of the molecular pathogenesis of myotonic dystrophy type 1 and myotonic.
[59]
Non-invasive prenatal diagnosis (NIPD): how analysis of cell ... - NIH
Nov 16, 2022 · The presence of this cffDNA in the maternal bloodstream has enabled clinical implementation of non-invasive prenatal diagnosis (NIPD) for monogenic disorders.
[60]
Genetics of Myotonic Dystrophy and FSHD
The genetic test for DM locates the specific area on chromosome 19 and measures the size of the DNA expansion. This test has nearly a 100% rate of accuracy in ...
[61]
Medical Genetics Practice Resources Test - ACMG
One pillar of ACMG's strategic plan is to develop and publish standards and guidelines that enhance the practice of medical genetics.
[62]
Electrodiagnostic Evaluation of Myopathies - PMC - PubMed Central
In DM2, electrical myotonia is seen distally in the arms, but it often affects both the proximal and distal leg muscles. Finally, classic waxing-waning ...
[63]
Cardiac Involvement and Arrhythmias Associated with Myotonic ...
In this review, we describe the cardiac manifestations of myotonic dystrophy with an emphasis on arrhythmia which is the second most common cause of death in ...Missing: supportive endocrine neuroimaging
[64]
An evaluation of 24 h Holter monitoring in patients with myotonic ...
Jul 19, 2022 · To evaluate the clinical effectiveness of routine 24 h Holter monitoring to screen for conduction disturbances and arrhythmias in patients with myotonic ...
[65]
Evaluation of echocardiography monitoring in myotonic dystrophy ...
Jul 1, 2025 · The aim of this study is to evaluate the long-term prevalence of LV dysfunction during echocardiographic follow-up of patients with DM1.
[66]
Assessment of Respiratory Function and Need for Noninvasive ...
Jun 18, 2022 · Respiratory function in DM1 patients is characterized by progressive inspiratory and expiratory muscle weakness, which causes a restrictive ...
[67]
Evaluation of Sleep-Disordered Breathing and Respiratory ...
Apr 15, 2025 · This study aimed to explore the outcomes of pulmonary function tests and sleep-disordered breathing (SDB) workups in children with DM1 and to ...
[68]
Current Progress in CNS Imaging of Myotonic Dystrophy - PMC
Neuroimaging in myotonic dystrophies provided a major contribution to the insight into brain involvement which is highly prevalent in these multisystemic ...
[69]
Clinical Care Recommendations for Cardiologists Treating Adults ...
Feb 6, 2020 · This document represents expert opinion derived from cardiologists with experience treating cardiac complications in myotonic dystrophy.Missing: classification | Show results with:classification
[70]
Drug treatment for myotonia - PMC - PubMed Central - NIH
Three participants with myotonic dystrophy and treated with phenytoin or carbamazepine had cardiac side effects (ventricular tachycardia and ...
[71]
Mexiletine is an effective antimyotonia treatment in myotonic ...
May 3, 2010 · Conclusions: Mexiletine at dosages of 150 and 200 mg 3 times daily is effective, safe, and well-tolerated over 7 weeks as an antimyotonia ...
[72]
Mexiletine in Myotonic Dystrophy Type 1 - NIH
Our trial confirms and extends the results of a prior clinical trial by demonstrating that mexiletine reduces hand grip myotonia in patients with DM1. Hand grip ...
[73]
What medicines are useful to treat myotonia (delayed muscle ...
Apr 8, 2025 · Mexiletine appears to be safe and is likely an effective treatment for managing symptoms of myotonia (delayed muscle relaxation after a contraction)
[74]
Carbamazepine versus diphenylhydantoin in the ... - PubMed
Both dosages of PHT and CBZ induced a significant improvement of myotonia. For PHT a trend towards decreased efficacy is pointed out at toxic or at high dosages ...
[75]
2021 PACES Expert Consensus Statement on the Indications and ...
Jul 29, 2021 · Permanent pacemaker implantation is reasonable in patients with myotonic dystrophy type 1 for marked first-degree AV block (PR interval >240 ...
[76]
[PDF] Consensus-based Care Recommendations for Cardiologists ...
Preventing sudden cardiac death is of high priority in the care of patients with myotonic dystrophy type 1 (DM1). Such deaths in DM1 are mostly attributable to ...
[77]
Comprehensive Cardiovascular Management of Myotonic Dystrophy ...
Beta-blockers should be reserved for patients without AV conduction abnormalities or recipients of PM and/or ICD; the up-titrate drug dosage should be applied ...
[78]
Myotonic Dystrophy - OpenAnesthesia
May 30, 2023 · Neostigmine should be avoided for reversal of neuromuscular blockade as it may exacerbate myotonia. · Prolonged emergence can be expected due to ...
[79]
[PDF] PRACTICAL SUGGESTIONS FOR THE ANESTHETIC ...
Risks of anesthesia in Myotonic Dystrophy are most significant in the post-anesthesia period, but can be controlled by appropriate management.
[80]
Noninvasive respiratory assistance as aid for respiratory care ... - NIH
The use of noninvasive ventilation and mechanically assisted cough can reduce symptoms of hypoventilation, slow lung function decline, improve sleep quality,
[81]
Medical Management of Myotonic Dystrophy
Nov 22, 2017 · Clinicians may recommend that affected patients use a bilevel positive airway pressure device (BiPAP) for breathing assistance, especially at ...
[82]
Respiratory Management of Patients With Neuromuscular Weakness
Mar 13, 2023 · For patients with NMD and reduced cough effectiveness, we suggest manually assisted cough techniques independently or added to other modalities ...
[83]
[PDF] Consensus-based Care Recommendations for Pulmonologists ...
for respiratory support. c. Manual and/or mechanical cough assistance techniques (e.g., breath stacking, abdominal thrust, mechanical insufflator ...
[84]
Therapeutic advances in type 1 myotonic dystrophy complicated ...
Myotonic Dystrophy (DM) is a hereditary muscle disorder characterized by progressive muscle weakness, myotonia, and multi-system dysfunction.
[85]
Diabetes in Myotonic Dystrophy | Books Gateway - Karger Publishers
For individuals with myotonic dystrophy that have diabetes, treatment should be similar to that of individuals without myotonic dystrophy. Low-dose metformin ...
[86]
Myotonic dystrophy type 1 with diabetes mellitus, mixed ... - PubMed
Jan 18, 2018 · Glycemic control improved after modification of insulin sensitizers, such as metformin and pioglitazone. Hypogonadism was treated with ...
[87]
Ocular Features and Clinical Approach to Cataract and Corneal ...
Aug 25, 2022 · DM1 and DM2 share several features with the main distinction being prominent distal weakness and atrophy in DM1 versus primarily proximal in DM2 ...
[88]
Strategies for Preventing Intraoperative Miosis
May 20, 2015 · Careful preoperative planning can enable surgeons to maintain mydriasis even in eyes with known risks for intraoperative miosis, clinical research shows.
[89]
Consensus-based care recommendations for adults with myotonic ...
◦ Some DM2 patients have significant breathing problems that can result from muscle weakness of the diaphragm, abdominal and intercostal muscles, and myotonia ...
[90]
What is known about the effects of exercise or training to reduce ...
Mar 5, 2019 · Twenty-one papers were selected for in-depth analysis. Different exercise or training protocols were found including: acute exercise, ...<|control11|><|separator|>
[91]
[PDF] ROLE OF PHYSICAL THERAPY IN THE ASSESSMENT AND ...
Orthotic fit is often difficult because people with myotonic dystrophy have muscular wasting, and bony landmarks often become more prominent and susceptible to ...
[92]
Medical Management for Adult-Onset DM1/DM2 and Juvenile-Onset ...
This section addresses medical management of the many symptoms of adult-onset DM1 and DM2, as well as childhood-onset DM1.
[93]
Precision orthotics: optimising ankle foot orthoses to improve gait in ...
Feb 28, 2017 · To improve gait and reduce walking EC, patients with calf muscle weakness can be provided with an orthosis that restrains ankle dorsiflexion, ...
[94]
Mobility Aids & Orthotic Devices for Muscular Dystrophy
An orthotic device is a brace made to support weakened muscles. Braces can help keep the muscles flexible, which aids in slowing the progression of contractures ...
[95]
[PDF] Care Guidelines for Speech and Language Pathologists Treating ...
Nov 5, 2018 · Recommendations for speech and language therapy for myotonic dystrophy ... Swallowing: Therapy of Adults with Myotonic Dystrophy and Preserving ...
[96]
Interventions for dysphagia in long‐term, progressive muscle disease
Currently, the main interventions for managing oral feeding difficulties that can lead to dysphagia include dietary manipulation, adoption of safe ...
[97]
Chronic muscle stimulation improves muscle function and reverts ...
The results of this pilot study show that neuromuscular electrical stimulation (NMES) in patients affected by Myotonic Dystrophy type 1 and Congenital Myotonia ...
[98]
Current Treatment Options for Patients with Myotonic Dystrophy Type 2
Sep 27, 2021 · The previous phase II study with orally administered metformin showed a significant improvement of mobility in DM1 patients expressed by ...
[99]
Myotonic Muscular Dystrophy - Johns Hopkins Medicine
Supporting laboratory studies may include blood work, electrodiagnostic testing (EMG) and muscle biopsy. ... A test of lung function will also be performed.Missing: Holter sleep CK
[100]
Preimplantation genetic diagnosis for myotonic dystrophy type 1 - NIH
Preimplantation genetic diagnosis (PGD) is an alternative to prenatal diagnosis for patients at risk of transmitting an inherited disease such as myotonic ...
[101]
Myotonic dystrophy type 1 testing, 2024 revision: A technical ...
Jun 5, 2024 · Therefore, challenges for the genetic counseling of individuals and families affected by DM1 include extreme clinical variability, somatic ...Missing: CCUG | Show results with:CCUG
[102]
Neuropsychological and Psychological Functioning Aspects in ...
Introduction: Myotonic Dystrophy Type 1 (DM1) is an autosomal dominant genetic illness, characterized by a progressive loss of strength.Missing: issues | Show results with:issues
[103]
Family communication following a diagnosis of myotonic dystrophy ...
Aug 5, 2019 · This study explored the experiences of New Zealand families communicating about a diagnosis of type 1 myotonic dystrophy (DM1).
[104]
Myotonic Dystrophy Family Registry
The Myotonic Dystrophy Family Registry is unique in that it not only helps researchers find new, effective treatments and identify possible participants.
[105]
[PDF] Consensus-based Care Recommendations for Children with ...
Once the diagnosis is confirmed, refer to an expert multi-disciplinary myotonic dystrophy team to coordinate care, prioritize symptom management and make ...
[106]
Consensus-based care recommendations for adults with myotonic ...
○ Refer DM1 patients with respiratory symptoms including ineffective cough (normal peak expiratory cough flow rate is >270 L/min), respiratory insufficiency, ...
[107]
Prognosis and causes of death in myotonic dystrophy type 1 in our ...
Results: The mean age at death was 57.4±8.2 in all 24 years, 54.5±9.5 in the first half period, and 59.1±6.9 in the latter half period.
[108]
Survival in myotonic dystrophy type 1: a long time follow up-study ...
The median age at death was 55.7 years (range 32.5–79.0). Patients with the congenital form of the disease died at a lower age (45.2 years vs. 56.4, P = 0.01), ...
[109]
Congenital Myotonic Dystrophy - StatPearls - NCBI Bookshelf - NIH
Cognitive impairment correlates with the severity of weakness, size of CTG repeat, and maternal transmission. Sleep: excessive sleep disorder and sleep apnea ...
[110]
Age and causes of death in adult-onset myotonic dystrophy - PubMed
The cause of death could be determined in 70 of the 83 deceased patients. Pneumonia and cardiac arrhythmias were the most frequent primary causes of death ...
[111]
Multiorgan Involvement and Mortality in Individuals With Adult‐Onset ...
Apr 8, 2025 · The median survival age for individuals with adult DM1 is < 60 years, with pneumonia and cardiac involvement as the most frequent causes of ...
[112]
Milestones of progression in myotonic dystrophy type 1 and type 2
Median survival in DM1 was 70 years vs. 80 years in DM2 (hazard ratio 3.45, 95% CI 2.41 to 4.92, p < 0.0001; Suppl. Figure 1). Table ...
[113]
Core Clinical Phenotypes in Myotonic Dystrophies - PMC
May 2, 2018 · Myotonic dystrophy type 1 (DM1) and type 2 (DM2) represent the most frequent multisystemic muscular dystrophies in adulthood.
[114]
Entry - #160900 - MYOTONIC DYSTROPHY 1; DM1 - (OMIM.ORG)
Disease severity varies with the number of repeats: normal individuals have 5 to 37 repeats, mildly affected persons have 50 to 150 repeats, patients with ...
[115]
CTG repeat length underlying cardiac events and sudden death in ...
Regarding the cardiac events and mortality in patients with DM1, patients with 1300 or longer CTGn are at especially high risk. Keywords: Myotonic dystrophy, ...
[116]
Multisystem Symptoms in Myotonic Dystrophy Type 1
Implementing healthy lifestyle changes concerning diet and exercise, along with the appropriate use of various medications, can help regulate blood glucose ...
[117]
Cognitive impairment, neuroimaging abnormalities, and their ...
Myotonic dystrophy (DM) encompasses a spectrum of neuromuscular diseases characterized by myotonia, muscle weakness, and wasting. Recent research has led to the ...
[118]
Neuropsychological and Psychological Functioning Aspects in ...
Sep 19, 2018 · Introduction: Myotonic Dystrophy Type 1 (DM1) is an autosomal dominant genetic illness, characterized by a progressive loss of strength.
[119]
Living with myotonic dystrophy; what can be learned from couples ...
People with MD1 associate this progressive, neuromuscular condition with decreasing abilities, describing physical, cognitive and psychosocial barriers to ...
[120]
Global Prevalence of Myotonic Dystrophy: An Updated Systematic ...
The pooled estimate of the prevalence of DM1 was 9.27 cases (95% CI: 4.73 ... The pooled estimate of the prevalence of DM2 was 2.29 cases (95% CI: 0.17 ...
[121]
Anatomy of a founder effect: myotonic dystrophy in Northeastern ...
Dominantly transmitted myotonic dystrophy (DM1) is highly prevalent in SLSJ where its carrier rate reaches 1/550, compared with 1/5,000 to 1/50,000 elsewhere.
[122]
Global Prevalence of Myotonic Dystrophy: An Updated Systematic ...
Apr 28, 2022 · The overall prevalence of DM1 per 100,000 was estimated as 12.25 cases (95% CI: 7.50–18.06) in Europe and 3.61 cases (95% CI: 0.58–9.09) in ...Abstract · Introduction · Methods · ResultsMissing: France | Show results with:France
[123]
Population frequency of myotonic dystrophy: higher than expected ...
Myotonic dystrophy (DM) is the most common adult-onset muscular dystrophy with an estimated prevalence of 1/8000. There are two genetically distinct types, DM1 ...Missing: incidence | Show results with:incidence
[124]
a possible explanation for its absence in sub-Saharan Africa - PubMed
Ethnicity and myotonic dystrophy: a possible explanation for its absence in sub-Saharan Africa. Ann Hum Genet. 1996 Jan;60(1):57-65. doi: 10.1111/j.1469 ...Missing: variations Asians
[125]
Myotonic dystrophy type 2 is rare in the Japanese population - Nature
Jan 19, 2012 · Our study confirms that DM2 is an extremely rare cause of myotonic and/or LGMD patients in Japan. Although the spectrum of clinical presentation ...
[126]
Myotonic dystrophy: Pathology - Neuromuscular Home Page
MYOTONIC DYSTROPHY. DM1 DM2. Myotonic Dystrophy 1 (DM1). Chronic Late Mild, Rossolimo "De la myotonie atrophique" 1902. DM1: Adult, Chronic changes. Muscle ...Missing: 1901 | Show results with:1901
[127]
Myotonic dystrophy | MedLink Neurology
Myotonic dystrophies type 1 and 2 are inherited multisystem disorders marked by muscle weakness, myotonia, cataracts, and cardiac and cognitive issues.…
[128]
Anticipation in myotonic dystrophy: new light on an old problem - PMC
Anticipation in myotonic ... Harper P. S., Shaw D. J. Detection of linkage disequilibrium between the myotonic dystrophy locus and a new polymorphic DNA marker.Missing: chromosome 19
[129]
Myotonic dystrophy | Neurology
Aug 1, 1975 · 1 Nov 1986. Tight linkage of apolipoprotein C2 to myotonic dystrophy on chromosome 19 ... anticipation in families with linkage to chromosome ...
[130]
Proximal myotonic myopathy. Clinical features of a ... - PubMed - NIH
Proximal myotonic myopathy is a new genetic disorder similar to, but distinct from, DM. Patients suspected of having DM but with negative DNA studies may have ...Missing: 1990 | Show results with:1990
[131]
[PDF] English Translation of Dr. Hans Steinert's Initial Descriptions of ...
In 1904, Dr. Steinert, then an Associate Professor at Leipzig Medical Hospital, presented three cases of myotonia congenita Thomsen, complicated by a ...